Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury (ACTIVATE-AKI)

• ClinicalTrials.gov Identifier: NCT02962102
• Recruitment Status: Completed
• First Posted: November 11, 2016
• Results First Posted: February 3, 2022
• Last Update Posted: February 3, 2022
• Sponsor: David Leaf
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): David Leaf, Brigham and Women's Hospital

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy of calcifediol (25-hydroxyvitamin D) and calcitriol (1,25-dihydroxyvitamin D) in preventing and reducing the severity of acute kidney injury (AKI) in critically ill patients.

Condition or disease	Intervention/treatment	Phase
Critically Ill; Acute Kidney Injury	Drug: Calcifediol; Drug: Calcitriol; Drug: Placebos	Phase 2

Detailed Description:

Decreased circulating levels of active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are common in critically ill patients, and lower levels are independently associated with a higher risk of acute kidney injury (AKI). Further, administration of 25D and 1,25D attenuates AKI in animal models. The purpose of this study is to assess if administration of 25D and 1,25D decreases the incidence and severity of AKI in critically ill patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury (ACTIVATE-AKI)
• Actual Study Start Date: April 3, 2017
• Actual Primary Completion Date: July 16, 2020
• Actual Study Completion Date: August 6, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Calcifediol; Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4	Drug: Calcifediol; Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4
Experimental: Calcitriol; Calcitriol 4mcg orally daily x 5 days	Drug: Calcitriol; Calcitriol 4mcg orally daily x 5
Placebo Comparator: Placebo; Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days	Drug: Placebos; Placebo (medium chain triglyceride oil) orally daily x 5

Outcome Measures

Primary Outcome Measures :

1. Death Within 7 Days [ Time Frame: 7 days ]
   All-cause mortality within 7 days following randomization
2. Number of Participants Who Received Renal Replacement Therapy Within 7 Days [ Time Frame: 7 days ]
   Number of participants who received renal replacement therapy within 7 days following randomization
3. Relative Average Change in Serum Creatinine From Day 0 to Days 1-7 [ Time Frame: 7 days ]
   Average percentage change in serum creatinine assessed on days 1-7 as compared to day 0

Secondary Outcome Measures :

1. Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines [ Time Frame: 7 days ]
   Any of the following: 1) an increase in serum creatinine ≥50% compared to the immediate pre-randomization value; 2) new or progressive stage of oliguria; or 3) receipt of renal replacement therapy. Oliguria stages 1, 2, and 3 are defined as urine output (UOP) <0.5 ml/kg/h for 6-12h, <0.5 ml/kg/h for >12h, and <0.3 ml/kg/h for ≥24h or anuria for ≥12h, respectively.
2. Peak Serum Creatinine (mg/dl) [ Time Frame: 7 days ]
   Highest serum creatinine value on days 1 to 7
3. 28-day Mortality [ Time Frame: 28 days ]
   All-cause mortality assessed during the 28 days following randomization
4. ICU- and Hospital-free Days [ Time Frame: 28 days ]
   28 minus the number of days in the ICU or hospital, with 0 assigned to patients who die before 28 days

Other Outcome Measures:

1. Kidney Injury - Subgroup Analysis Based on Time Zero 25-hydroxyvitamin D Level Above Versus Below the Median [ Time Frame: 7 days ]
   Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days
2. Kidney Injury - Subgroup Analysis Based on the Presence or Absence of AKI on Enrollment [ Time Frame: 7 days ]
   Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days
3. Kidney Injury - Subgroup Analysis Based on APACHE II Score on Enrollment Above Versus Below the Median [ Time Frame: 7 days ]
   Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days
4. Kidney Injury - Subgroup Analysis Based on ICU Type (Medical Versus Surgical) [ Time Frame: 7 days ]
   Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days
5. Kidney Injury - Subgroup Analysis Based on the Presence or Absence of Sepsis on Enrollment [ Time Frame: 7 days ]
   Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18
• Admitted to the ICU within 48h prior to enrollment
• Likely to remain in the ICU (alive) for ≥72h
• Naso/orogastric tube or ability to swallow
• High risk of severe AKI

Exclusion Criteria:

• Serum total calcium > 9.0 mg/dl or phosphate > 6.0 mg/dL within previous 48h
• Currently receiving oral calcium supplementation
• Ingestion of vitamin D3 >1,000 IU/day or any 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D during the previous 7 days
• AKI stage 2 or 3 (based on KDIGO serum creatinine and/or urine output criteria)
• History of transplantation or receiving chronic (>7days) of immunosuppressive medications (not including glucocorticoid steroids at a dose less than or equivalent to prednisone 20 mg/day)
• Neutropenia in the previous 48h
• Active primary parathyroid disease, active granulomatous disease, or symptomatic nephrolithiasis in the previous 3 months
• Receiving cytochrome P450 inhibitors
• Chronic Kidney Disease stage V or End Stage Renal Disease
• Hemoglobin < 7 g/dL
• GI malabsorption
• Prisoner
• Pregnancy or breast feeding

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

David Leaf

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: David E Leaf, MD, MMSc; Brigham and Women's Hospital

  Study Documents (Full-Text)

Documents provided by David Leaf, Brigham and Women's Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] December 25, 2018

Informed Consent Form  [PDF] December 25, 2018

More Information

• Responsible Party: David Leaf, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT02962102
• Other Study ID Numbers: 2016P002527; 5K23DK106448 ( U.S. NIH Grant/Contract )
• First Posted: November 11, 2016
• Results First Posted: February 3, 2022
• Last Update Posted: February 3, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acute Kidney Injury; Critical Illness; Wounds and Injuries; Disease Attributes; Pathologic Processes; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Calcitriol; Calcifediol; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents; Vitamins; Micronutrients; Bone Density Conservation Agents